Changes in substrate metabolism and effects of excess fatty acids in reperfused myocardium.

Abstract

The purpose of these studies was to characterize the rates of fatty acid oxidation in reperfused myocardium and test the influence of excess fatty acids (FA) on mechanical function in the extracorporeally perfused, working swine heart model. Seventeen animals were prepared. Eight were untreated (LOW FA group; serum FA averaged 0.55 +/- 0.07 mumol/ml) and nine received a constant infusion of 10% Intralipid with heparin to raise serum FA to about 1.4 +/- 0.21 mumol/ml (HIGH FA group). Coronary flow in both groups was held at aerobic levels for an equilibrium period of 40 minutes, acutely reduced regionally in the anterior descending circulation by 60% for 45 minutes, and acutely restored to aerobic levels for 60-minute reflow. Appreciable mechanical depression (-47 delta% from aerobic values; p less than 0.01) during reperfusion was noted in both groups. This was associated with modest reductions in myocardial oxygen consumption (p less than 0.05) and losses of total tissue carnitine stores (p at least less than 0.02). Reperfused myocardium showed a strong preference for and aerobic use of FA during reflow such that 14CO2 production from labeled palmitate exceeded preischemic levels (+89 delta% in LOW FA hearts; +111 delta% in HIGH FA hearts). This suggested relative preservation of restoration of certain elements in mitochondrial function during reflow. The findings argue for uncoupling between substrate metabolism and energy production, accelerated but useless energy drainage, or some impairment between energy transfer and function of contractile proteins as possible explanations for the persistent depression of mechanical function (stunning) during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Intralipid infusion ameliorates propranolol-induced hypotension in rabbits

“…A strong preference for, and aerobic use of, fatty acids as substrate has been demonstrated in isolated working swine hearts undergoing reperfusion post-stunning [29]. Myocardial substrate preference under conditions of increased lactate concentration is known to shift toward greater oxidation of free fatty acids [30].…”

The Suppression of Proinflammatory Cytokines Improves Heart Function From Non-Heart-Beating Donors Following Transplantation in a Canine Model

“…Immediately after reperfusion, anaerobic metabolism in the reperfused myocardium continues, and glucose continues to be the main source of energy. 31,32) Therefore, it is believed that the histopathological findings in this study demonstrate that the shift from glucose utilization under anaerobic conditions to fatty acid utilization under restored aerobic conditions after reperfusion may have occurred more rapidly in the FR-2 group than in the control group. These results suggest that suppressing proinflammatory cytokines such as TNF-α and IL-1β before both ischemia in the donor and reperfusion in the recipient effectively preserves cardiac function with NHBDs.…”

“…The normal myocardium depends mainly on fatty acids for its energy source under aerobic conditions, whereas it uses principally glucose under anaerobic conditions. [31][32][33] The amount of glycogen stored in the myocardium decreases after a period of ischemia and recovers gradually after reperfusion. Immediately after reperfusion, anaerobic metabolism in the reperfused myocardium continues, and glucose continues to be the main source of energy.…”

Myocardial Insulin Resistance: An Overview of Its Causes, Effects, and Potential Therapy

“…During early ischaemia there is a transient increase in anaerobic glycolysis while glucose oxidation decreases [199,[221][222][223][224]. Under these conditions normal or increased glucose uptake (under the influence of insulin) may be important for the delivery of glycolytic ATP to maintain ion homeostasis.…”